Based on the anatomical studies we have proposed a "contact theory" for the function of the juxtaglomerular apparatus. This theory for which we have no direct experimental evidence could explain, however, a great deal of the experimental information obtained by the physiologists. In this project we want to provide experimental support for the theory. By changing the rate of renin secretion by previously well established methods, we hope to be able to visualize correlative changes in the space separating the vascular and tubular components of the JGA. In order to preserve the in vivo orientation of these structures, we will freeze the tissue, then freeze-dry and embed directly in plastic (42,43). We have reasonable expectations that this method will be applicable to kidney. We also define an experimental approach for the rigorous definition of the chemical nature of the renal nerves. Our definition will be based on histochemical, electron microscopic and autoradiographic data. Concentrative work will be done on the rat although monkeys and rabbits will also be used whenever possible. The last specific objective will be the isolation of the JGA granule fraction from rabbit renal cortex homogenates by means of zonal centrifugation, further purify by centrifugation and biochemically analyze to determine the enzymatic content of the purified JGA granules and use the isolated granules for further studies.